Alzheimer's disease (AD) is a chronic neurodegenerative disease that primarily affects the elderly and for which there are currently only symptomatic treatments. Early pathological features of the AD brain include mitochondrial and synaptic dysfunction, which is considered to be related to progressive amyloid-beta (Aβ) oligomer accumulation in synaptic mitochondria. This affects membrane potential, membrane permeability transition pore (mPTP) formation, respiration, energy metabolism, oxidative stress, mitochondrial dynamics and calcium homeostasis. Since mitochondrial dysfunction is believed to play a role in Aβ-induced toxicity, a compound that restores this dysfunction might have potential therapeutic benefit. Thus, Aβ oligomer inhibitors or procedures for blocking Aβ oligomer production appear to offer promising approaches for prevention and treatment of AD. Cyclophilin D (CypD), a peptidyl prolyl isomerase F, resides in the mitochondrial matrix, associates with the inner mitochondrial membrane and plays a central role in opening the mitochondrial mPTP leading to cell death. Neurons in AD-affected regions of the brain have significantly elevated levels of CypD.
Therefore, it may be advantageous to inhibit CypD in order to inhibit the effects of and provide treatments for AD. CypD is also known to positively effects of diabetes.